What were the latest results from this trial?

Tagawa: This is an update of the phase II portion of a phase I/II trial. Of about 40 patients participating, 36 are evaluable for response — which is the primary endpoint. With the increased numbers, the response rate has held up and remains above 30 percent. This is a nice benchmark against historical chemotherapy in patients who were pretreated with chemotherapy, as it is pretty rare to get a response rate above ten percent.

Besides just having a nice objective response rate, the intent-to-treat analysis included patients who didn't necessarily make it to a scan or have early progression. The overall intent-to-treat analysis showed that progression-free survival is above seven months and overall survival above 15 months, which goes hand-in-hand with the response rate.

Overall, it’s a well-tolerated drug. And, as I am speaking right now, I have a patient in New York receiving month 20 of therapy, so he's had, essentially, a complete response in his liver and has tolerated therapy for 20 months. We see myelosuppression, that being the dose-limiting toxicity, but it’s completely manageable.

With an ADC, we'd expect more delivery to the tumor area and less systemically. Some of the side effects we might see with irinotecan, such as diarrhea, is generally grade 1, occasionally grade 2 [with Sacituzumab govitecan]. So, I think in concept, the ADC delivering more to the tumor — or the tumor area in this case — and less to the systemic circulation, holds up with the ADC.

Even though preliminary, the objective response rates and progression-free and overall survival all look impressive versus historical control. So, I think ADCs are one additional exciting modality of therapy.

What are the next steps with sacituzumab govitecan?

The next step would be to complete the total phase II trial, so we are close. We hope to have completion of enrollment within the next couple of months and then have the final results later in the year.

If the results hold up, we would call this a positive phase II trial and that would set the stage for a phase III trial, which we've talked about but haven't fully designed yet.

What other treatments, including immunotherapy, are emerging in the landscape of urothelial carcinoma?

Broadly, in the terms of metastatic urothelial carcinoma, we've had platinum-based therapy for a long period of time. I think some people forget that about one in ten patients, historically, have had long-term or disease control or cures just with platinum-based chemotherapy. So, I think that remains important to remember.

What has moved from "very exciting" to primetime, are checkpoint inhibitors, with the approval of a couple agents recently, and more coming in 2017. Specifically, PD-1 and PD-L1 antibodies are very nice because they are generally very well tolerated. Those patients that respond can have a very durable response, whether they remain on therapy or not.

The unfortunate part is that it is only around a quarter of all patients that do respond, so we'd like to work on that with biomarkers to select patients, as well as a way to increase the number of patients who respond. But now the unmet need is beyond just platinum-based therapy and a single PD-1 or PD-L1 antibody.

What I find exciting are several ADCs — IMMU-132 being one — that have now treated above 40 patients. So, I find that as a group, they all seem to be fairly well tolerated. They are all nonrandomized trials, but this is compared to historical controls of chemotherapy.

There are other regimens, as well, such as Cyramza (ramucirumab) in combination with chemotherapy, which is finishing a phase III trial, so we'll see about those results. FGFR3 targeting also looks pretty exciting, and it’s possible that we are going to have one or two of those drugs in the next few years.